Over a million unintended pregnancies occur in the USA each year because of either discontinuation or misuse of contraceptives. Long-acting progestin-only contraceptives (LAPC) sub-dermal implants and intrauterine devices are ideal contraceptives since they are long acting, do not require strict adherence to a daily pill, or the discomfort of a patch or vaginal ring and because they are free from the thrombotic risks attendant estrogen-containing combined hormonal contraceptives. However, the major reason for discontinuation of LAPCs is the occurrence of unpredictable, intermittent, abnormal uterine bleeding (AUB). Discovering molecular/cellular targets that contribute to LAPC-induced AUB is essential to creating better contraceptive formulations.